Modulation of immune dysfunction during murine leukaemia retrovirus infection of old mice by dehyroepiandrosterone sulphate (DHEAS)

Abstract

SUMMARYAgeing, leukaemia and acquired immune deficiency syndrome (AIDS ) are conditions with dysregulated cytokine production. As dehydroepiandrosterone sulphate (DHEAS ) restored normal cytokine production in old mice its effects on retrovirally infected old mice were investigated. Retrovirus infection and ageing-induced immune dysfunction. Murine retrovirus-infected old C57BL/6 female mice consumed 0·22 or 0·44 mg of DHEAS/mouse/day beginning 2 weeks postinfection for 10 weeks. DHEAS largely prevented the retrovirus-induced reduction in T-cell and B-cell mitogenesis. DHEAS supplement prevented loss of cytokines [interleukin-2 (IL-2) and interferon-c] secretion by mitogen-stimulated splenocytes representing T helper 1 (Th1) cell phenotypes. It also suppressed the retrovirus-induced, excessive production of cytokines (IL-6 and IL-10) by Th2 cells. The highest dose of DHEAS reduced IL-6 production by splenocytes from uninfected old mice by 75% while increasing their IL-2 secretion by nearly 50%. Thus immune dysfunction induced by ageing, even when exacerbated by murine retrovirus infection, was largely prevented by DHEAS.

Dehydroepiandrosterone Sulphate Enhances IgG and Interferon-Gamma Production During Immunization to Tuberculosis in Young But not Aged Mice

“…In this study, both aged and young animals immunized with mycHSP70 and DHEAS presented significantly higher levels of IFN-c. This corroborates previous data showing increased IFN-c levels in retrovirus-infected aged C57/BL6 mice that received DHEAS orally (Araghi-Niknam et al 1997). It has been shown that immunization to proteins in IFA or alum as adjuvants induced polarized Th2 immune responses in neonatal and young adult mice, characterized by the production of antigenspecific IL-4, IL-5, IgG1 and IgE, but not IFN-c or IgG2a (Chu et al 1997;Yip et al 1999).…”

T cells and aging (update February 1999)

“…It also decreases the spontaneous secretion of IL 6 (576) and IL 10 observed in old mice and reverses their hypersensitivity to endotoxin-stimulated release of both IL 6 and IL 10 (577), and enhances lymphocyte activation (578). Analogously, it prevents the retrovirus-induced increased IL 6 and IL 10 secretion seen in old mice, prevents decreases of IL 2 and IFN-gamma production and enhances their T and B cell proliferative responses (579). IL 6 may be the critical cytokine here, because treating aged mice with IL 6-but not IL 1-neutralizing antibody resulted in a reversion of their cytokine production pattern to that characteristic of young animals (580).…”

Effects of Whole-Body Gamma Irradiation and 5-Androstenediol Administration on Serum G-CSF

“…(12,13) The 5-androstene steroids provide resistance to infection by stimulating immune responses. (14)(15)(16)(17) Based on the fact that these steroids enhance resistance to infection after administration in animals, (14)(15)(16)(17) we evaluated these steroids for their radioprotective efficacy in the mouse model against cobalt-60 gamma irradiation. We observed that single injections of 5-AED 24 to 48 hr before or 2 hr after whole body gamma irradiation significantly enhanced survival, increased granulocytemonocyte progenitors in bone marrow, and elevated numbers of granulocytes, monocytes, natural killer cells, platelets, and erythrocytes in peripheral blood.…”